Color Doppler twinkling artifact in fetuses with echogenic intracardiac foci: echocardiographic observation and clinical significance.

OBJECTIVE: To evaluate echocardiographic characteristics and clinical relevance of color Doppler twinkling artifacts in fetuses with isolated echogenic intracardiac foci (EIF). METHODS: This study included 50 fetuses with EIF, at 18-38 weeks of gestation. Echocardiographic examination, which was performed using a 1.0-5.0-MHz phased array probe, included gray-scale, color and spectral Doppler imaging. Twinkling artifacts were assessed using fetal color Doppler echocardiography on isolated EIF situated in the left and/or right ventricles. The prevalence, appearance and clinical relevance of the color Doppler twinkling artifacts were analyzed. RESULTS: Eight of 50 fetuses with EIF (16%) showed color Doppler twinkling artifacts, which appeared as a rapidly changing color complex seen persistently behind the EIF. The spectra obtained in all eight with color Doppler artifacts were composed of straight vertical bands occurring in mid to late systole and early diastole. After birth, none of 50 fetuses with EIF had structural heart diseases or showed clinical signs of cardiac failure. CONCLUSIONS: Color Doppler twinkling artifacts from isolated EIF occur in some fetuses and may be considered as an additional echocardiographic feature of EIF. Attention should be paid to the identification and interpretation of these artifacts so that they may be accurately distinguished from true color flow generated by atrioventricular valvular regurgitation jets.

Effects of phenylalanine and its metabolites on cytoplasmic free calcium in cortical neurons.

Classic phenylketonuria (PKU) is characterized by brain lesions. However, its underlying neurotoxic mechanisms remain unknown. Based on our previous studies, we hypothesized that calcium might participate in PKU-associated neuropathy. In cultured cortical neurons, cytoplasmic free calcium concentration ([Ca(2+)](i)) decreased dramatically when treatment with phenylalanine (Phe) and phenyllactic acid, while phenylacetic acid treatment immediately increased [Ca(2+)](i), which began to decrease after 3 min. Moreover, [Ca(2+)](i) decreased dramatically after Phe treatment in the presence of EGTA suggesting that Phe might increase [Ca(2+)](i) efflux. Phe-induced [Ca(2+)](i) decrease was strongly inhibited by vanadate, a non-specific plasma membrane Ca(2+)-ATPase (PMCA) antagonist, suggesting that Phe might increase [Ca(2+)](i) efflux throught modulating PMCA. These findings were further supported by the facts that Phe could increase membrance (45)Ca-uptake capability and PMCA activity. In contrast, treatment of KBR7943 or thapsigargin, antagonists to Na/Ca Exchanger (NCX) and Sarco/Endoplasmic reticulum Ca(2+)-ATPase (SERCA), respectively, did not elicit any changes in [Ca(2+)](i). Specific siRNA against PMCA had an effect similar to vanadate. Since the brain injury induced by phenylalaninemia was thought to be a chronic process, we cultured cortical neurons in the presence of Phe for 2 weeks and measured [Ca(2+)](i), PMCA activity and (45)Ca-uptake capability at days 3, 7, 9 and 14, respectively. PMCA activity and (45)Ca-uptake capability decreased from day 9, at the same time [Ca(2+)](i) increase was observed. In conclusion, PMCA participate in regulating Phe-induced initial rapid decrease in [Ca(2+)](i) and subsequent long-term increase in [Ca(2+)](i).